The goal of this research proposal is to increase the understanding of the cellular processes involved in the renewal of the outer segments of vertegrate photoreceptor cells. These cells play a critical role in the visual process and are involved, either directly or indirectly, in several important pathological conditons prevalent in humans, such as retinitis pigmentosa and senile macular degeneration. The process of outer segment renewal represents the major metabolic task of the photoreceptor and thus has been assumed to be of critical functional importance to it. Several specific aspects of outer segment renewal in the retinas of a variety of species will be studied. The examination of a variety of species, including several mammals, is considered important since the lact of correlative species information is a major weakness in the current understanding of outer segment renewal mechanisms. The methodologies to be used are light and electron microscopy. Using a rectified polarizing microscope with video contrast enhancement, the following will be studied: (a) the quantitative aspects of the longitudinal variations in birefringence in the rod outersegments of amphibia, (b) the longitudinal variations in several molecular constituents of rod outer segment membranes which might give rise to the observed variations in birefringence, and (c) the occurrence of periodic variations in birefringence in isolated outer segments from a variety of species (including goldfish, pigeon, mouse, rat and rabbit). Using the electron microscope, the study will investigate (a) the path of opsin migration through the photoreceptor by examination of inner segment membrane systems and their associated intramembranous particles in freeze-fracture replicas from both conventionally fixed and quick-frozen retinas, (b) the involvement and control of membrane fusion events in the transport of outer segment precursors to their sites of assembly, (c) the involvement in these fusion events of a structure found in some photoreceptors similar to one present in the frog neuromuscular junction and shown there to be involved in controlling the fusion of transmitter containing vesicles, and (d) the possible molecular mechanisms subserving the apparent absence of the inner segment plasma membrane.